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Relative Importance of Lean Mass and Fat Mass on Bone Mineral Density in a Group of Lebanese Postmenopausal Women
Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 14, no. 3, 326e331, 2011 Ó Copyright 2011 by The International Society for Clinical Densitometry 1094-6950/14:326e331/$36.00 DOI: 10.1016/j.jocd.2011.04.002
Original Article
Relative Importance of Lean Mass and Fat Mass on Bone Mineral Density in a Group of Lebanese Postmenopausal Women Rawad El Hage,*,1 Christophe Jacob,1 Elie Moussa,1 and Rafic Baddoura2 1
Laboratoire de physiologie et de biomecanique de la performance motrice, Universite de Balamand, Al Koura, Liban; and 2Department of Rheumatology, H^otel-Dieu Hospital, St Joseph University, Beirut, Lebanon
Abstract The aim of this study was to determine the relative importance of lean mass and fat mass on bone mineral density (BMD) in a group of Lebanese postmenopausal women. One hundred ten Lebanese postmenopausal women (aged 65e84 yr) participated in this study. Age and years since menopause were recorded. Body weight and height were measured and body mass index (BMI) was calculated. Body composition (lean mass, fat mass, and fat mass percentage) was assessed by dual-energy X-ray absorptiometry (DXA). Bone mineral content (BMC) of the whole body (WB) and BMD of the WB, the lumbar spine (L1eL4), the total hip (TH), the femoral neck (FN), the ultra distal (UD) Radius, and the 1/3 Radius were measured by DXA. The expressions WB BMC/height and WB BMD/ height were also used. Weight, BMI, fat mass, and lean mass were positively correlated to WB BMC, WB BMC/ height, WB BMD/height, and to WB, L1eL4, TH, FN, UD Radius, and 1/3 Radius BMD. However, using multiple linear regression analyses, fat mass was more strongly correlated to BMC and to BMD values than lean mass after controlling for years since menopause. This study suggests that fat mass is a stronger determinant of BMC and BMD than lean mass in Lebanese postmenopausal women. Key Words: Adiposity; bone mass; hormones; Lebanon; osteoporosis.
factors, mechanical factors (e.g., practicing impact sports), or the exposure to deleterious influences (10). Low calcium and vitamin D intake and high prevalence of sedentary lifestyle among Lebanese subjects may partially explain the low values of BMD in this country (11e15). Usually, body weight is closely related to BMD (1,10). However, there is a significant disagreement in the literature regarding the relative contributions of the lean and fat components of body weight (16e19). Interestingly, fat has been shown to be a strong determinant of BMD in postmenopausal women (18e23). In fact, adipocytes are important sources of estrogen derived from aromatization in the postmenopausal period (16,19e21). Moreover, the insulin resistance of fat cells may increase circulating free sex hormones such as estrogen (19e21). These 2 mechanisms may explain the positive association between fat mass and bone mass in postmenopausal women (19e21). In contrast, osteoblasts in the bone marrow are replaced by adipocytes in the postmenopausal period. Furthermore, increased bone marrow fat is negatively associated to trabecular bone volume (16). Indeed, in the bone marrow,
Introduction Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, leading to decreased bone strength and increased evidence of fragility fractures (1). BMD is the best single predictor of fracture risk especially in postmenopausal women (2). In clinical practice, BMD measurements are widely used to diagnose osteoporosis (1e12). This disease is common among Arab and Lebanese women (2e9). In actual fact, BMD values for Lebanese subjects are lower compared with the American/European subjects (3,5). The factors contributing to the variance in BMD values are genetics, race, gender, dietary intakes (e.g., calcium intake), endocrine Received 01/24/11; Revised 02/14/11; Accepted 04/02/11. *Address correspondence to: Rawad El Hage, PhD, Faculty of Art and Social Sciences, Division of Physical Education, University of Balamand, P.O. Box: 100 Tripoli, Lebanon. E-mail: [email protected]
326
Body Composition and BMD in Postmenopausal Women peroxisome proliferator-activated receptor-gamma (PPAR-y) stimulates adipocyte differentiation but inhibits osteoblast development from mesenchymal stem cells. In vivo, increased PPAR-y activity leads to bone loss (16). The aim of this study was to explore the relative contribution of lean mass and fat mass to BMD in a group of Lebanese postmenopausal women.
Material and Methods Subjects One hundred ten Lebanese postmenopausal women (aged 65e84 yr) participated in this study. Women were randomly selected from the greater Beirut area. The estimated resident population of Beirut is around 1 million (a mixture of the various Lebanese communities) (7). Age and years since menopause were recorded.
Exclusion Criteria Any medical condition likely to affect bone metabolism such as the history of major chronic disease, the intake of medications that affect bone metabolism, history of steroid intake for more than 6 mo, treatment with bisphosphonates, selective estrogen-receptor modulators, calcitonin or hormone replacement therapy for more than 1 yr during the previous 5 yr were excluded. Also excluded were subjects with the history of bed rest for more than 1 mo within 6 mo before the study, subjects with previous surgery on the spine or both hips, and those with the history of radiotherapy or chemotherapy. Subjects with conditions technically interfering with dual-energy X-ray absorptiometry (DXA) BMD assessment were also excluded, that is, previous surgery on the spine, hip, forearm, or an imaging contrast procedure within the past week. The study was approved by the Institutional Review Board of the American University of Beirut, and informed consent was obtained from all the study participants (7).
Anthropometric Measurements Height (cm) was measured in the upright position to the nearest 1 mm with a Seca standard stadiometer. Body weight (kg) was measured on a Taurus mechanic scales with a precision of 100 g. Women were weighed wearing only underclothes. Body mass index (BMI) was calculated as body weight divided by height squared (kg/m2). Body composition (lean mass, fat mass, body fat percentage) was assessed by DXA (Hologic QDR-4500 W; Waltham, MA). In our center, the in vivo coefficients of variation were !1% for fat and lean mass.
Bone Mass Measurements Bone mineral content (BMC, g), bone mineral area (cm2), and density (BMD, g/cm2) were determined for each individual. The DXA measurements were completed for the whole body (WB), the lumbar spine (L1eL4), the total hip (TH), the femoral neck (FN), the ultra distal (UD) Radius, and the 1/3 Radius using the instrument previously described. In our center, the coefficients of variation were !1.5% for BMC and BMD (6,7). The expressions WB BMC/height and WB Journal of Clinical Densitometry: Assessment of Skeletal Health
327 BMD/height were calculated to adjust for WB bone size (24e26). The same certified technician performed all analyses using the same technique for all the measurements.
Statistical Analysis The means and standard deviations were calculated for all the clinical data and for the bone measurements. Associations between clinical and bone data were given as Pearson correlation coefficients. Multiple linear regression analysis models were used to test the relationship between bone data (BMC, BMD, BMC/height, and BMD/height) with years since menopause, lean mass, and fat mass and r2 were reported. Data were analyzed with Number Cruncher Statistical System (2001). A level of significance of p ! 0.05 was used.
Results Clinical Characteristics and Bone Measurements of the Subjects Age, years since menopause, anthropometric characteristics, and bone data (WB BMC, WB BMC/height, WB BMD,
Table 1 Clinical Characteristics and Bone Data of the Study Population Parameter Age (yr) Years since menopause (yr) Weight (kg) Height (cm) BMI (kg/m2) Fat mass (kg) Fat mass/height (kg/cm) Fat mass (%) Lean mass (kg) Lean mass/height (kg/cm) WB BMC (g) WB BMC/height (g/cm) WB BMD (g/cm2) WB BMD/height (g/cm2/cm) L1eL4 BMD (g/cm2) Total hip BMD (g/cm2) Femoral neck BMD (g/cm2) UD Radius BMD (g/cm2) 1/3 Radius BMD (g/cm2)
Mean SD
Range
72.2 5.1 23.2 4.1 69.1 14.0 151.8 6.3 29.9 5.5 26.9 8.3 0.178 0.053 39.0 6.1 40.5 6.1 0.258 0.036 1,501 315 9.8 1.9 0.880 0.094 0.0058 0.0006
65e84 16e35 37e105 132e172 19.2e48.9 7.2e46.4 0.052e0.308 19.6e50.3 26.6e55.2 0.195e0.356 742e2,446 5.1e15.1 0.679e1.21 0.0046e0.0075
0.791 0.159 0.718 0.137 0.621 0.108
0.504e1.27 0.344e1.06 0.352e1.01
0.310 0.065
0.162e0.488
0.527 0.079
0.339e0.721
Abbr: SD, standard deviation; BMI, Body Mass Index; WB, whole body; BMC, bone mineral content; BMD, bone mineral density; UD, ultra distal. Volume 14, 2011
Abbr: YSM, years since menopause; BMI, Body Mass Index; WB, whole body; BMC, bone mineral content; BMD, bone mineral density; TH, total hip; FN, femoral neck; UD, ultra distal. *p ! 0.05. **p ! 0.01. ***p ! 0.001.
0.26** 0.43*** 0.21* 0.40*** 0.40*** 0.40*** 0.30** 0.39*** 0.38*** 0.42*** 0.49*** 0.31** 0.41*** 0.47*** 0.44*** 0.35*** 0.44*** 0.39*** 0.32*** 0.62*** 0.28** 0.57*** 0.63*** 0.62*** 0.56*** 0.48*** 0.44*** 0.05 0.41*** 0.17 0.39*** 0.37*** 0.36*** 0.25** 0.34*** 0.34*** 0.15 0.36*** 0.14 0.47*** 0.36*** 0.40*** 0.30** 0.23* 0.30* 0.25** 0.52*** 0.25* 0.48*** 0.48*** 0.47*** 0.36*** 0.41*** 0.40*** 0.31** 0.68*** 0.34*** 0.62*** 0.66*** 0.64*** 0.52*** 0.56*** 0.52*** 0.35*** 0.71*** 0.51*** 0.57*** 0.66*** 0.62*** 0.51*** 0.61*** 0.53*** YSM (yr) Weight (kg) Height (cm) BMI (kg/m2) Fat mass (kg) Fat mass/height (kg/cm) Fat mass (%) Lean mass (kg) Lean mass/height (kg/cm)
FN BMD (g/cm2) WB BMC WB BMC/ WB BMD WB BMD/height L1eL4 BMD TH BMD (g) height (g/cm) (g/cm2) (g/cm2/cm) (g/cm2) (g/cm2) Parameter
Table 2 Correlations Between Clinical Characteristics and Bone Data
0.24* 0.43*** 0.16 0.43*** 0.40*** 0.41*** 0.35*** 0.35*** 0.35***
El Hage et al. 1/3 Radius UD Radius BMD (g/cm2) BMD (g/cm2)
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Journal of Clinical Densitometry: Assessment of Skeletal Health
WB BMD/height, L1eL4 BMD, TH BMD, FN BMD, UD Radius BMD, and 1/3 Radius BMD) are displayed in Table 1.
Associations Between Clinical Characteristics and Bone Data Weight, BMI, fat mass, fat mass percentage, and lean mass were all positively correlated to bone data (WB BMC, WB BMC/height, WB BMD, WB BMD/height, L1eL4 BMD, TH BMD, FN BMD, UD Radius BMD, and 1/3 Radius BMD) ( p ! 0.05). Height was positively correlated to WB BMC, WB BMC/height, WB BMD, TH BMD, FN BMD, and 1/3 Radius BMD ( p ! 0.05). WB BMC, WB BMC/height, WB BMD, TH BMD, FN BMD, 1/3 Radius BMD, and UD Radius BMD were negatively correlated to years since menopause ( p ! 0.05; Table 2). Figure 1 shows the relation between fat mass and TH BMD. Figure 2 shows the relation between lean mass and TH BMD. Figure 3 shows the relation between fat mass and the ratio WB BMD/height. Figure 4 shows the relation between lean mass and the ratio WB BMD/height. Figure 5 shows the relation between fat mass/height and TH BMD. Figure 6 shows the relation between lean mass/ height and TH BMD.
Multivariate Analysis Lean mass was not significantly related to WB, TH, and FN BMD after controlling for years since menopause and fat mass (Table 3). Fat mass was a better determinant of WB BMC than lean mass after controlling for years since menopause (Table 3). Finally, lean mass was not significantly related to WB BMC/height, TH BMD, UD Radius BMD, and WB BMD/height after controlling for fat mass and years since menopause.
Discussion This study conducted on 110 Lebanese postmenopausal women shows that fat mass is a stronger determinant of BMC and BMD than lean mass. This result is clinically
Fig. 1. Relation between fat mass and total hip (TH) bone mineral density (BMD). Volume 14, 2011
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Fig. 2. Relation between lean mass and total hip (TH) bone mineral density (BMD).
Fig. 4. Relation between lean mass and whole body (WB) bone mineral density (BMD)/height.
important because it suggests that obesity may have a protective role against osteoporosis in Lebanese postmenopausal women. In this report, BMC and BMD values were negatively correlated to years since menopause. It is well established that the menopausal period is associated with an important bone loss (1e9). Identifying the determinants of BMC and BMD in this period of life is clinically important especially in Lebanese postmenopausal women because they have lower BMD values when compared with Americans and Europeans (5e7). In our study, body weight and BMI were positively correlated to BMC and BMD. These data confirm previous reports that BMD is closely related to body weight and BMI in postmenopausal women (20,27e29). Several mechanisms may explain the weight-BMD relationship in this period of life (20,21,26). Indeed, BMI is inversely related to osteoclast activity in normal postmenopausal women (19). Furthermore, weight loss and fasting for many days are associated with a decreased osteoblastic activity (20). We found that lean mass and fat mass were positively associated with BMC and BMD. However, fat mass was a stronger determinant of bone parameters (BMC, BMD, BMC/ height, and BMD/height) than lean mass. These results are in
line with those reported by Reid (19). Furthermore, fat mass was found to be a negative determinant of bone loss during the postmenopausal period (30,31). Fat mass may influence bone tissue by 2 different mechanisms (19). Firstly, increased fat mass augments mechanical loading on the skeleton. Secondly, a number of hormones may link the 2 tissues (20). For instance, being overweight is associated with an increased aromatization of androgen to estrogen in adipose tissue, decreased sex hormone-binding globulin with increased free sex steroids, hyperleptinemia, and hyperinsulinemia (19,20,26). Estrogen, insulin, and leptin are well known to stimulate bone formation (19,20). Moreover, amylin and preptin that are co-secreted with insulin stimulate osteoblast proliferation in vitro (19). Another potential mechanism for fat is its effect as absorber of environmental toxins thus protecting other tissues from their harmful effect (32e34). A larger fat mass leads to a lower circulation of environmental toxins thus reducing their negative impact on bone during bone formation years (32e34). In general, the fat-BMD relationship depends on gender (the fat-bone relationship is weaker in men), menopausal status (the fat-bone relationship is stronger in postmenopausal
Fig. 3. Relation between fat mass and whole body (WB) bone mineral density (BMD)/height.
Fig. 5. Relation between fat mass/height and total hip (TH) bone mineral density (BMD).
Journal of Clinical Densitometry: Assessment of Skeletal Health
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El Hage et al. and visceral fat have different effects on bone structure and strength (38). Finally, we did not assess several determinants of BMC and BMD such as physical activity, daily calcium intake, protein intake, and vitamin D status. Nevertheless, up to our knowledge, it’s the first study that aimed at exploring the relative importance of lean and fat mass to BMD in Lebanese postmenopausal women. In conclusion, because fat mass was found to be a stronger determinant of BMC and BMD than lean mass in this population, we suggest that obesity may have a protective role against osteoporosis and bone loss in Lebanese postmenopausal women.
Fig. 6. Relation between lean mass/height and total hip (TH) bone mineral density (BMD). women), and exercise status (the relationship is stronger in sedentary populations) (19,25,26,35,36). Our study has some limitations. Firstly, the cross-sectional nature of this study is a limitation because it cannot evaluate the confounder variables. Secondly, our study sample may not be representative of the general population of Lebanese postmenopausal women. Thirdly, DXA cannot distinguish between subcutaneous and visceral fat, or between subcutaneous and intramuscular peripheral fat (37). However, subcutaneous
Table 3 Multiple Linear Regression Analysis Models Parameter
Coefficient
SE
p
Dependent variable: WB BMC (r2 5 0.50) Constant 774 197 Fat mass (kg) 16.4 3.6 Lean mass (kg) 14 4.8 Years since menopause 11.4 4.4
0.0002 !0.0001 0.005 0.01
Dependent variable: WB BMD (r2 5 0.24) Constant 0.743 0.072 Fat mass (kg) 0.003 0.001 Lean mass (kg) 0.002 0.001 Years since menopause 0.002 0.001
!0.0001 0.003 0.22 0.13
Dependent variable: TH BMD (r2 5 0.43) Constant 0.541 Fat mass (kg) 0.009 Lean mass (kg) 0.001 Years since menopause 0.005
0.093 0.001 0.002 0.002
!0.0001 !0.0001 0.56 0.01
Dependent variable: FN BMD (r2 5 0.33) Constant 0.560 Fat mass (kg) 0.003 Lean mass (kg) 0.003 Years since menopause 0.007
0.080 0.001 0.001 0.001
!0.0001 0.01 0.10 0.0002
Abbr: WB, whole body; BMC, bone mineral content; BMD, bone mineral density; TH, total hip; FN, femoral neck; SE, standard error. Journal of Clinical Densitometry: Assessment of Skeletal Health
References 1. Rizzoli R, Bonjour JP, Ferrari SL. 2001 Osteoporosis, genetics and hormones. J Mol Endocrinol 26:79e94. 2. Marshall D, Johnell O, Wedel H. 1996 Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254e1259. 3. Hammoudeh M, Al-Khayarin M, Zirie M, Bener A. 2005 Bone density measured by dual energy X-ray absorptiometry in Qatari women. Maturitas 52:319e327. 4. Sadat-Ali M, Al-Habdan IM, Al-Mulhim FA, El-Hassan AY. 2004 Bone mineral density among postmenopausal Saudi women. Saudi Med J 25:1615e1623. 5. El-Hajj Fuleihan G, Baddoura R, Awada H, et al. 2002 Low peak bone mineral density in healthy Lebanese subjects. Bone 31: 520e528. 6. Baddoura R, Awada H, Okais J, et al. 2006 An audit of bone densitometry practice with reference to ISCD, IOF and NOF guidelines. Osteoporos Int 17:1111e1115. 7. Baddoura R, Arabi A, Haddad-Zebouni S, et al. 2007 Vertebral fracture risk and impact of database selection on identifying elderly Lebanese with osteoporosis. Bone 40:1066e1072. 8. Baddoura R, Okais J, Awada H. 2001 Incidence fracturaire apres 50 ans et implications d’osteoporose dans la population Libanaise. Rev Epidemiol Sante Publique 49:27e32. 9. Baddoura R. 2001 Incidence of hip fractures in the Lebanese population. East Mediterr Health J 7:725e729. 10. Rizzoli R. 2006 Determinants of peak bone mass. Ann Endocrinol (Paris) 67:114e115. 11. El-Hajj Fuleihan G, Deeb M. 1999 Hypovitaminosis D in a sunny country. N Engl J Med 340:1840e1841. 12. El-Hajj Fuleihan G, Nabulsi M, Shoucair M, et al. 2001 Hypovitaminosis D in healthy school children. Pediatrics 107:1e7. 13. El Hage R, Jacob C, Moussa E, et al. 2009 Daily calcium intake and body mass index in a group of Lebanese adolescents. J Med Liban 57:253e257. 14. Fazah A, Jacob C, Moussa E, et al. 2010 Activity, inactivity and quality of life among Lebanese adolescents. Pediatr Int 52: 573e578. 15. El Bcheraoui C, Chapuis-Lucciani N. 2008 Obesity in the Lebanese elderly: prevalence, relative risks and anthropometrical measurements. J Med Liban 56:174e180. 16. Rosen CJ, Klibanski A. 2009 Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med 122:409e414. 17. Doyle F, Brown J, Lachance C. 1970 Relation between bone mass and muscle weight. Lancet 1:391e393. 18. Khosla S, Atkinson EJ, Riggs BL, Melton LJ. 1996 Relationship between body composition and bone mass in women. J Bone Miner Res 11:857e863. Volume 14, 2011
Body Composition and BMD in Postmenopausal Women 19. Reid IR. 2010 Fat and bone. Arch Biochem Biophys 503:20e27. 20. Reid IR. 2002 Relationships among body mass, its components, and bone. Bone 31:547e555. 21. Ho-Pham LT, Nguyen ND, Lai TQ, Nguyen TV. 2010 Contributions of lean mass and fat mass to bone mineral density: a study in postmenopausal women. BMC Musculoskelet Disord 11:59. 22. Compston JE, Bhambhani M, Laskey MA, et al. 1992 Body composition and bone mass in post-menopausal women. Clin Endocrinol (Oxf) 37:426e431. 23. Reid IR, Evans MC, Ames RW. 1994 Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal women. Osteoporos Int 4:362e367. 24. Bachrach LK, Hastie T, Wang MC, et al. 1999 Bone mineral acquisition in healthy Asian, Hispanic, Black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab 84: 4702e4712. 25. Reid IR, Lindsay DP, Margaret CE. 1992 Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endocrinol Metab 75:779e782. 26. Reid IR, Ames R, Evans MC, et al. 1992 Determinants of total body and regional bone mineral density in normal postmenopausal women-a key role for fat mass. J Clin Endocrinol Metab 75:45e51. 27. Ravn P, Cizza G, Bjarnason NH, et al. 1999 Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. J Bone Miner Res 14:1622e1627. 28. De Laet C, Kanis JA, Oden A, et al. 2005 Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16: 1330e1338. 29. Gnudi S, Sitta E, Fiumi N. 2007 Relationship between body composition and bone mineral density in women with and without osteoporosis: relative contribution of lean and fat mass. J Bone Miner Metab 25:326e332.
Journal of Clinical Densitometry: Assessment of Skeletal Health
331 30. Reid IR, Ames RW, Evans MC, et al. 1994 Determinants of the rate of bone loss in normal postmenopausal women. J Clin Endocrinol Metab 79:950e954. 31. Wu F, Ames R, Clearwater J, et al. 2002 Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy. Clin Endocrinol (Oxf) 56:703e711. 32. Cho MR, Shin JY, Hwang JH, et al. 2011 Associations of fat mass and lean mass with bone mineral density differ by levels of persistent organic pollutants: National Health and Nutrition Examination Survey 1999-2004. Chemosphere 82: 1268e1276. 33. Van der Ven LT, van de Kuil T, Leonards PE, et al. 2009 Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reproduction study in Wistar rats. Toxicol Lett 185:51e62. 34. Lind PM, Milnes MR, Lundberg R, et al. 2004 Abnormal bone composition in female juvenile American alligators from a pesticide-polluted lake (Lake Apopka, Florida). Environ Health Perspect 112:359e362. 35. El Hage R, Courteix D, Benhamou CL, et al. 2009 Relative importance of lean and fat mass on bone mineral density in a group of adolescent girls and boys. Eur J Appl Physiol 105: 759e764. 36. Wang MC, Bachrach LK, Van Loan M, et al. 2005 The relative contributions of lean tissue mass and fat mass to bone density in young women. Bone 37:474e481. 37. Bolotin HH, Siev€anen H. 2001 Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral density can seriously mislead diagnostic/prognostic interpretations of patient-specific bone fragility. J Bone Miner Res 16:799e805. 38. Gilsanz V, Chalfant J, Mo AO, et al. 2009 Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94:3387e3393.
Volume 14, 2011
Original Article
Relative Importance of Lean Mass and Fat Mass on Bone Mineral Density in a Group of Lebanese Postmenopausal Women Rawad El Hage,*,1 Christophe Jacob,1 Elie Moussa,1 and Rafic Baddoura2 1
Laboratoire de physiologie et de biomecanique de la performance motrice, Universite de Balamand, Al Koura, Liban; and 2Department of Rheumatology, H^otel-Dieu Hospital, St Joseph University, Beirut, Lebanon
Abstract The aim of this study was to determine the relative importance of lean mass and fat mass on bone mineral density (BMD) in a group of Lebanese postmenopausal women. One hundred ten Lebanese postmenopausal women (aged 65e84 yr) participated in this study. Age and years since menopause were recorded. Body weight and height were measured and body mass index (BMI) was calculated. Body composition (lean mass, fat mass, and fat mass percentage) was assessed by dual-energy X-ray absorptiometry (DXA). Bone mineral content (BMC) of the whole body (WB) and BMD of the WB, the lumbar spine (L1eL4), the total hip (TH), the femoral neck (FN), the ultra distal (UD) Radius, and the 1/3 Radius were measured by DXA. The expressions WB BMC/height and WB BMD/ height were also used. Weight, BMI, fat mass, and lean mass were positively correlated to WB BMC, WB BMC/ height, WB BMD/height, and to WB, L1eL4, TH, FN, UD Radius, and 1/3 Radius BMD. However, using multiple linear regression analyses, fat mass was more strongly correlated to BMC and to BMD values than lean mass after controlling for years since menopause. This study suggests that fat mass is a stronger determinant of BMC and BMD than lean mass in Lebanese postmenopausal women. Key Words: Adiposity; bone mass; hormones; Lebanon; osteoporosis.
factors, mechanical factors (e.g., practicing impact sports), or the exposure to deleterious influences (10). Low calcium and vitamin D intake and high prevalence of sedentary lifestyle among Lebanese subjects may partially explain the low values of BMD in this country (11e15). Usually, body weight is closely related to BMD (1,10). However, there is a significant disagreement in the literature regarding the relative contributions of the lean and fat components of body weight (16e19). Interestingly, fat has been shown to be a strong determinant of BMD in postmenopausal women (18e23). In fact, adipocytes are important sources of estrogen derived from aromatization in the postmenopausal period (16,19e21). Moreover, the insulin resistance of fat cells may increase circulating free sex hormones such as estrogen (19e21). These 2 mechanisms may explain the positive association between fat mass and bone mass in postmenopausal women (19e21). In contrast, osteoblasts in the bone marrow are replaced by adipocytes in the postmenopausal period. Furthermore, increased bone marrow fat is negatively associated to trabecular bone volume (16). Indeed, in the bone marrow,
Introduction Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, leading to decreased bone strength and increased evidence of fragility fractures (1). BMD is the best single predictor of fracture risk especially in postmenopausal women (2). In clinical practice, BMD measurements are widely used to diagnose osteoporosis (1e12). This disease is common among Arab and Lebanese women (2e9). In actual fact, BMD values for Lebanese subjects are lower compared with the American/European subjects (3,5). The factors contributing to the variance in BMD values are genetics, race, gender, dietary intakes (e.g., calcium intake), endocrine Received 01/24/11; Revised 02/14/11; Accepted 04/02/11. *Address correspondence to: Rawad El Hage, PhD, Faculty of Art and Social Sciences, Division of Physical Education, University of Balamand, P.O. Box: 100 Tripoli, Lebanon. E-mail: [email protected]
326
Body Composition and BMD in Postmenopausal Women peroxisome proliferator-activated receptor-gamma (PPAR-y) stimulates adipocyte differentiation but inhibits osteoblast development from mesenchymal stem cells. In vivo, increased PPAR-y activity leads to bone loss (16). The aim of this study was to explore the relative contribution of lean mass and fat mass to BMD in a group of Lebanese postmenopausal women.
Material and Methods Subjects One hundred ten Lebanese postmenopausal women (aged 65e84 yr) participated in this study. Women were randomly selected from the greater Beirut area. The estimated resident population of Beirut is around 1 million (a mixture of the various Lebanese communities) (7). Age and years since menopause were recorded.
Exclusion Criteria Any medical condition likely to affect bone metabolism such as the history of major chronic disease, the intake of medications that affect bone metabolism, history of steroid intake for more than 6 mo, treatment with bisphosphonates, selective estrogen-receptor modulators, calcitonin or hormone replacement therapy for more than 1 yr during the previous 5 yr were excluded. Also excluded were subjects with the history of bed rest for more than 1 mo within 6 mo before the study, subjects with previous surgery on the spine or both hips, and those with the history of radiotherapy or chemotherapy. Subjects with conditions technically interfering with dual-energy X-ray absorptiometry (DXA) BMD assessment were also excluded, that is, previous surgery on the spine, hip, forearm, or an imaging contrast procedure within the past week. The study was approved by the Institutional Review Board of the American University of Beirut, and informed consent was obtained from all the study participants (7).
Anthropometric Measurements Height (cm) was measured in the upright position to the nearest 1 mm with a Seca standard stadiometer. Body weight (kg) was measured on a Taurus mechanic scales with a precision of 100 g. Women were weighed wearing only underclothes. Body mass index (BMI) was calculated as body weight divided by height squared (kg/m2). Body composition (lean mass, fat mass, body fat percentage) was assessed by DXA (Hologic QDR-4500 W; Waltham, MA). In our center, the in vivo coefficients of variation were !1% for fat and lean mass.
Bone Mass Measurements Bone mineral content (BMC, g), bone mineral area (cm2), and density (BMD, g/cm2) were determined for each individual. The DXA measurements were completed for the whole body (WB), the lumbar spine (L1eL4), the total hip (TH), the femoral neck (FN), the ultra distal (UD) Radius, and the 1/3 Radius using the instrument previously described. In our center, the coefficients of variation were !1.5% for BMC and BMD (6,7). The expressions WB BMC/height and WB Journal of Clinical Densitometry: Assessment of Skeletal Health
327 BMD/height were calculated to adjust for WB bone size (24e26). The same certified technician performed all analyses using the same technique for all the measurements.
Statistical Analysis The means and standard deviations were calculated for all the clinical data and for the bone measurements. Associations between clinical and bone data were given as Pearson correlation coefficients. Multiple linear regression analysis models were used to test the relationship between bone data (BMC, BMD, BMC/height, and BMD/height) with years since menopause, lean mass, and fat mass and r2 were reported. Data were analyzed with Number Cruncher Statistical System (2001). A level of significance of p ! 0.05 was used.
Results Clinical Characteristics and Bone Measurements of the Subjects Age, years since menopause, anthropometric characteristics, and bone data (WB BMC, WB BMC/height, WB BMD,
Table 1 Clinical Characteristics and Bone Data of the Study Population Parameter Age (yr) Years since menopause (yr) Weight (kg) Height (cm) BMI (kg/m2) Fat mass (kg) Fat mass/height (kg/cm) Fat mass (%) Lean mass (kg) Lean mass/height (kg/cm) WB BMC (g) WB BMC/height (g/cm) WB BMD (g/cm2) WB BMD/height (g/cm2/cm) L1eL4 BMD (g/cm2) Total hip BMD (g/cm2) Femoral neck BMD (g/cm2) UD Radius BMD (g/cm2) 1/3 Radius BMD (g/cm2)
Mean SD
Range
72.2 5.1 23.2 4.1 69.1 14.0 151.8 6.3 29.9 5.5 26.9 8.3 0.178 0.053 39.0 6.1 40.5 6.1 0.258 0.036 1,501 315 9.8 1.9 0.880 0.094 0.0058 0.0006
65e84 16e35 37e105 132e172 19.2e48.9 7.2e46.4 0.052e0.308 19.6e50.3 26.6e55.2 0.195e0.356 742e2,446 5.1e15.1 0.679e1.21 0.0046e0.0075
0.791 0.159 0.718 0.137 0.621 0.108
0.504e1.27 0.344e1.06 0.352e1.01
0.310 0.065
0.162e0.488
0.527 0.079
0.339e0.721
Abbr: SD, standard deviation; BMI, Body Mass Index; WB, whole body; BMC, bone mineral content; BMD, bone mineral density; UD, ultra distal. Volume 14, 2011
Abbr: YSM, years since menopause; BMI, Body Mass Index; WB, whole body; BMC, bone mineral content; BMD, bone mineral density; TH, total hip; FN, femoral neck; UD, ultra distal. *p ! 0.05. **p ! 0.01. ***p ! 0.001.
0.26** 0.43*** 0.21* 0.40*** 0.40*** 0.40*** 0.30** 0.39*** 0.38*** 0.42*** 0.49*** 0.31** 0.41*** 0.47*** 0.44*** 0.35*** 0.44*** 0.39*** 0.32*** 0.62*** 0.28** 0.57*** 0.63*** 0.62*** 0.56*** 0.48*** 0.44*** 0.05 0.41*** 0.17 0.39*** 0.37*** 0.36*** 0.25** 0.34*** 0.34*** 0.15 0.36*** 0.14 0.47*** 0.36*** 0.40*** 0.30** 0.23* 0.30* 0.25** 0.52*** 0.25* 0.48*** 0.48*** 0.47*** 0.36*** 0.41*** 0.40*** 0.31** 0.68*** 0.34*** 0.62*** 0.66*** 0.64*** 0.52*** 0.56*** 0.52*** 0.35*** 0.71*** 0.51*** 0.57*** 0.66*** 0.62*** 0.51*** 0.61*** 0.53*** YSM (yr) Weight (kg) Height (cm) BMI (kg/m2) Fat mass (kg) Fat mass/height (kg/cm) Fat mass (%) Lean mass (kg) Lean mass/height (kg/cm)
FN BMD (g/cm2) WB BMC WB BMC/ WB BMD WB BMD/height L1eL4 BMD TH BMD (g) height (g/cm) (g/cm2) (g/cm2/cm) (g/cm2) (g/cm2) Parameter
Table 2 Correlations Between Clinical Characteristics and Bone Data
0.24* 0.43*** 0.16 0.43*** 0.40*** 0.41*** 0.35*** 0.35*** 0.35***
El Hage et al. 1/3 Radius UD Radius BMD (g/cm2) BMD (g/cm2)
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WB BMD/height, L1eL4 BMD, TH BMD, FN BMD, UD Radius BMD, and 1/3 Radius BMD) are displayed in Table 1.
Associations Between Clinical Characteristics and Bone Data Weight, BMI, fat mass, fat mass percentage, and lean mass were all positively correlated to bone data (WB BMC, WB BMC/height, WB BMD, WB BMD/height, L1eL4 BMD, TH BMD, FN BMD, UD Radius BMD, and 1/3 Radius BMD) ( p ! 0.05). Height was positively correlated to WB BMC, WB BMC/height, WB BMD, TH BMD, FN BMD, and 1/3 Radius BMD ( p ! 0.05). WB BMC, WB BMC/height, WB BMD, TH BMD, FN BMD, 1/3 Radius BMD, and UD Radius BMD were negatively correlated to years since menopause ( p ! 0.05; Table 2). Figure 1 shows the relation between fat mass and TH BMD. Figure 2 shows the relation between lean mass and TH BMD. Figure 3 shows the relation between fat mass and the ratio WB BMD/height. Figure 4 shows the relation between lean mass and the ratio WB BMD/height. Figure 5 shows the relation between fat mass/height and TH BMD. Figure 6 shows the relation between lean mass/ height and TH BMD.
Multivariate Analysis Lean mass was not significantly related to WB, TH, and FN BMD after controlling for years since menopause and fat mass (Table 3). Fat mass was a better determinant of WB BMC than lean mass after controlling for years since menopause (Table 3). Finally, lean mass was not significantly related to WB BMC/height, TH BMD, UD Radius BMD, and WB BMD/height after controlling for fat mass and years since menopause.
Discussion This study conducted on 110 Lebanese postmenopausal women shows that fat mass is a stronger determinant of BMC and BMD than lean mass. This result is clinically
Fig. 1. Relation between fat mass and total hip (TH) bone mineral density (BMD). Volume 14, 2011
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Fig. 2. Relation between lean mass and total hip (TH) bone mineral density (BMD).
Fig. 4. Relation between lean mass and whole body (WB) bone mineral density (BMD)/height.
important because it suggests that obesity may have a protective role against osteoporosis in Lebanese postmenopausal women. In this report, BMC and BMD values were negatively correlated to years since menopause. It is well established that the menopausal period is associated with an important bone loss (1e9). Identifying the determinants of BMC and BMD in this period of life is clinically important especially in Lebanese postmenopausal women because they have lower BMD values when compared with Americans and Europeans (5e7). In our study, body weight and BMI were positively correlated to BMC and BMD. These data confirm previous reports that BMD is closely related to body weight and BMI in postmenopausal women (20,27e29). Several mechanisms may explain the weight-BMD relationship in this period of life (20,21,26). Indeed, BMI is inversely related to osteoclast activity in normal postmenopausal women (19). Furthermore, weight loss and fasting for many days are associated with a decreased osteoblastic activity (20). We found that lean mass and fat mass were positively associated with BMC and BMD. However, fat mass was a stronger determinant of bone parameters (BMC, BMD, BMC/ height, and BMD/height) than lean mass. These results are in
line with those reported by Reid (19). Furthermore, fat mass was found to be a negative determinant of bone loss during the postmenopausal period (30,31). Fat mass may influence bone tissue by 2 different mechanisms (19). Firstly, increased fat mass augments mechanical loading on the skeleton. Secondly, a number of hormones may link the 2 tissues (20). For instance, being overweight is associated with an increased aromatization of androgen to estrogen in adipose tissue, decreased sex hormone-binding globulin with increased free sex steroids, hyperleptinemia, and hyperinsulinemia (19,20,26). Estrogen, insulin, and leptin are well known to stimulate bone formation (19,20). Moreover, amylin and preptin that are co-secreted with insulin stimulate osteoblast proliferation in vitro (19). Another potential mechanism for fat is its effect as absorber of environmental toxins thus protecting other tissues from their harmful effect (32e34). A larger fat mass leads to a lower circulation of environmental toxins thus reducing their negative impact on bone during bone formation years (32e34). In general, the fat-BMD relationship depends on gender (the fat-bone relationship is weaker in men), menopausal status (the fat-bone relationship is stronger in postmenopausal
Fig. 3. Relation between fat mass and whole body (WB) bone mineral density (BMD)/height.
Fig. 5. Relation between fat mass/height and total hip (TH) bone mineral density (BMD).
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El Hage et al. and visceral fat have different effects on bone structure and strength (38). Finally, we did not assess several determinants of BMC and BMD such as physical activity, daily calcium intake, protein intake, and vitamin D status. Nevertheless, up to our knowledge, it’s the first study that aimed at exploring the relative importance of lean and fat mass to BMD in Lebanese postmenopausal women. In conclusion, because fat mass was found to be a stronger determinant of BMC and BMD than lean mass in this population, we suggest that obesity may have a protective role against osteoporosis and bone loss in Lebanese postmenopausal women.
Fig. 6. Relation between lean mass/height and total hip (TH) bone mineral density (BMD). women), and exercise status (the relationship is stronger in sedentary populations) (19,25,26,35,36). Our study has some limitations. Firstly, the cross-sectional nature of this study is a limitation because it cannot evaluate the confounder variables. Secondly, our study sample may not be representative of the general population of Lebanese postmenopausal women. Thirdly, DXA cannot distinguish between subcutaneous and visceral fat, or between subcutaneous and intramuscular peripheral fat (37). However, subcutaneous
Table 3 Multiple Linear Regression Analysis Models Parameter
Coefficient
SE
p
Dependent variable: WB BMC (r2 5 0.50) Constant 774 197 Fat mass (kg) 16.4 3.6 Lean mass (kg) 14 4.8 Years since menopause 11.4 4.4
0.0002 !0.0001 0.005 0.01
Dependent variable: WB BMD (r2 5 0.24) Constant 0.743 0.072 Fat mass (kg) 0.003 0.001 Lean mass (kg) 0.002 0.001 Years since menopause 0.002 0.001
!0.0001 0.003 0.22 0.13
Dependent variable: TH BMD (r2 5 0.43) Constant 0.541 Fat mass (kg) 0.009 Lean mass (kg) 0.001 Years since menopause 0.005
0.093 0.001 0.002 0.002
!0.0001 !0.0001 0.56 0.01
Dependent variable: FN BMD (r2 5 0.33) Constant 0.560 Fat mass (kg) 0.003 Lean mass (kg) 0.003 Years since menopause 0.007
0.080 0.001 0.001 0.001
!0.0001 0.01 0.10 0.0002
Abbr: WB, whole body; BMC, bone mineral content; BMD, bone mineral density; TH, total hip; FN, femoral neck; SE, standard error. Journal of Clinical Densitometry: Assessment of Skeletal Health
References 1. Rizzoli R, Bonjour JP, Ferrari SL. 2001 Osteoporosis, genetics and hormones. J Mol Endocrinol 26:79e94. 2. Marshall D, Johnell O, Wedel H. 1996 Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254e1259. 3. Hammoudeh M, Al-Khayarin M, Zirie M, Bener A. 2005 Bone density measured by dual energy X-ray absorptiometry in Qatari women. Maturitas 52:319e327. 4. Sadat-Ali M, Al-Habdan IM, Al-Mulhim FA, El-Hassan AY. 2004 Bone mineral density among postmenopausal Saudi women. Saudi Med J 25:1615e1623. 5. El-Hajj Fuleihan G, Baddoura R, Awada H, et al. 2002 Low peak bone mineral density in healthy Lebanese subjects. Bone 31: 520e528. 6. Baddoura R, Awada H, Okais J, et al. 2006 An audit of bone densitometry practice with reference to ISCD, IOF and NOF guidelines. Osteoporos Int 17:1111e1115. 7. Baddoura R, Arabi A, Haddad-Zebouni S, et al. 2007 Vertebral fracture risk and impact of database selection on identifying elderly Lebanese with osteoporosis. Bone 40:1066e1072. 8. Baddoura R, Okais J, Awada H. 2001 Incidence fracturaire apres 50 ans et implications d’osteoporose dans la population Libanaise. Rev Epidemiol Sante Publique 49:27e32. 9. Baddoura R. 2001 Incidence of hip fractures in the Lebanese population. East Mediterr Health J 7:725e729. 10. Rizzoli R. 2006 Determinants of peak bone mass. Ann Endocrinol (Paris) 67:114e115. 11. El-Hajj Fuleihan G, Deeb M. 1999 Hypovitaminosis D in a sunny country. N Engl J Med 340:1840e1841. 12. El-Hajj Fuleihan G, Nabulsi M, Shoucair M, et al. 2001 Hypovitaminosis D in healthy school children. Pediatrics 107:1e7. 13. El Hage R, Jacob C, Moussa E, et al. 2009 Daily calcium intake and body mass index in a group of Lebanese adolescents. J Med Liban 57:253e257. 14. Fazah A, Jacob C, Moussa E, et al. 2010 Activity, inactivity and quality of life among Lebanese adolescents. Pediatr Int 52: 573e578. 15. El Bcheraoui C, Chapuis-Lucciani N. 2008 Obesity in the Lebanese elderly: prevalence, relative risks and anthropometrical measurements. J Med Liban 56:174e180. 16. Rosen CJ, Klibanski A. 2009 Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med 122:409e414. 17. Doyle F, Brown J, Lachance C. 1970 Relation between bone mass and muscle weight. Lancet 1:391e393. 18. Khosla S, Atkinson EJ, Riggs BL, Melton LJ. 1996 Relationship between body composition and bone mass in women. J Bone Miner Res 11:857e863. Volume 14, 2011
Body Composition and BMD in Postmenopausal Women 19. Reid IR. 2010 Fat and bone. Arch Biochem Biophys 503:20e27. 20. Reid IR. 2002 Relationships among body mass, its components, and bone. Bone 31:547e555. 21. Ho-Pham LT, Nguyen ND, Lai TQ, Nguyen TV. 2010 Contributions of lean mass and fat mass to bone mineral density: a study in postmenopausal women. BMC Musculoskelet Disord 11:59. 22. Compston JE, Bhambhani M, Laskey MA, et al. 1992 Body composition and bone mass in post-menopausal women. Clin Endocrinol (Oxf) 37:426e431. 23. Reid IR, Evans MC, Ames RW. 1994 Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal women. Osteoporos Int 4:362e367. 24. Bachrach LK, Hastie T, Wang MC, et al. 1999 Bone mineral acquisition in healthy Asian, Hispanic, Black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab 84: 4702e4712. 25. Reid IR, Lindsay DP, Margaret CE. 1992 Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endocrinol Metab 75:779e782. 26. Reid IR, Ames R, Evans MC, et al. 1992 Determinants of total body and regional bone mineral density in normal postmenopausal women-a key role for fat mass. J Clin Endocrinol Metab 75:45e51. 27. Ravn P, Cizza G, Bjarnason NH, et al. 1999 Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. J Bone Miner Res 14:1622e1627. 28. De Laet C, Kanis JA, Oden A, et al. 2005 Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16: 1330e1338. 29. Gnudi S, Sitta E, Fiumi N. 2007 Relationship between body composition and bone mineral density in women with and without osteoporosis: relative contribution of lean and fat mass. J Bone Miner Metab 25:326e332.
Journal of Clinical Densitometry: Assessment of Skeletal Health
331 30. Reid IR, Ames RW, Evans MC, et al. 1994 Determinants of the rate of bone loss in normal postmenopausal women. J Clin Endocrinol Metab 79:950e954. 31. Wu F, Ames R, Clearwater J, et al. 2002 Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy. Clin Endocrinol (Oxf) 56:703e711. 32. Cho MR, Shin JY, Hwang JH, et al. 2011 Associations of fat mass and lean mass with bone mineral density differ by levels of persistent organic pollutants: National Health and Nutrition Examination Survey 1999-2004. Chemosphere 82: 1268e1276. 33. Van der Ven LT, van de Kuil T, Leonards PE, et al. 2009 Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reproduction study in Wistar rats. Toxicol Lett 185:51e62. 34. Lind PM, Milnes MR, Lundberg R, et al. 2004 Abnormal bone composition in female juvenile American alligators from a pesticide-polluted lake (Lake Apopka, Florida). Environ Health Perspect 112:359e362. 35. El Hage R, Courteix D, Benhamou CL, et al. 2009 Relative importance of lean and fat mass on bone mineral density in a group of adolescent girls and boys. Eur J Appl Physiol 105: 759e764. 36. Wang MC, Bachrach LK, Van Loan M, et al. 2005 The relative contributions of lean tissue mass and fat mass to bone density in young women. Bone 37:474e481. 37. Bolotin HH, Siev€anen H. 2001 Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral density can seriously mislead diagnostic/prognostic interpretations of patient-specific bone fragility. J Bone Miner Res 16:799e805. 38. Gilsanz V, Chalfant J, Mo AO, et al. 2009 Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94:3387e3393.
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